Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment, discount, and disutility

Abstract

Objective: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis.

Methods: A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs.

Results: Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient.

Conclusions: When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of confidential PAS discount.

Keywords:

• Multiple sclerosis
• fingolimod
• alemtuzumab
• cost-utility
• cost-effectiveness
• highly active relapsing-remitting multiple sclerosis

Transparency

Declaration of funding

This study was funded by Novartis Pharmaceuticals UK Limited, Camberley, UK.

Declaration of financial/other relationships

NA is a paid employee of Novartis Pharmaceuticals UK Ltd, Camberley, UK. RN is a paid employee of Imperial College Healthcare NHS Trust, London, UK, and has acted as a paid consultant in the past for Biogen, Roche, Teva, Merck, and Novartis. He has also received research funds from and worked on clinical trials run by Biogen and Novartis. RN did not receive financial compensation for authorship of this manuscript. SM and JK are paid employees of Costello Medical Consulting Ltd, Cambridge, UK, which was contracted by Novartis to undertake some of the work. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors take full responsibility for the content of the paper. No assistance in the preparation of this article is to be declared.